This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Amyloid-? (A?) peptides have a strong membrane-associated ability that can induce cytotoxicity to neurons by altering membrane integrity and permeability. However, the molecular mechanism underlying A? neurotoxicity, i.e. whether these peptides form ion channels/pores or induce membrane defects, remains unclear. The proposed work strives to establish a molecular-level relationship between oligomer structural transition from the aqueous to the membrane environment and their biological activity in cell membranes by comparing two states of oligomer structures (in solution vs. on membrane) and two types of membrane disruption mechanism (membrane integrity vs. ion-channel) for different A? oligomers with distinct structural morphology.